methyl 4-(fluoromethyl)benzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 200 ml of methanol, 8.68 g of methyl 4-(fluoromethyl)benzoate was dissolved, and 77 ml of aqueous solution of 1 N sodium hydroxide was added dropwise with stirring and cooling. The mixture was then stirred for 3.5 hours at room temperature. After the mixture was acidified with 1 N hydrochloric acid, the precipitated crystals were collected by filtration, and the filtrate was concentrated. The precipitated crystals were combined with the residue obtained by concentrating the filtrate, and water was added thereto. The mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to provide 7.47 g of the objective compound as colorless crystals. M.p. 192–194° C. cooling The mixture was then stirred for 3.5 hours at room temperature the precipitated crystals were collected by filtration the filtrate was concentrated obtained by concentrating the filtrate, and water was added The mixture was extracted with ethyl acetate dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dry acetonitrile (150 ml) was added to 25.00 g of methyl 4-(bromomethyl)benzoate, 19.02 g of potassium fluoride and 9.51 g of calcium fluoride, and the mixture was heated to reflux for 3 days. The reaction solution was concentrated. After addition of 200 ml of acetonitrile, insolubles were removed by filtration, and the filtrate was concentrated again. The residue was purified by silica gel column chromatography (YMC•GEL® SIL-60-230/70, n-hexane:ethyl acetate=10:1–4:1), followed by distillation under reduced pressure to provide 14.45 g of the objective compound as colorless oil. B.p. 118.5–119° C./18 mmHg. the mixture was heated to reflux for 3 days The reaction solution was concentrated After addition of 200 ml of acetonitrile, insolubles were removed by filtration the filtrate was concentrated again The residue was purified by silica gel column chromatography (YMC•GEL® SIL-60-230/70, n-hexane:ethyl acetate=10:1–4:1) followed by distillation under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dry acetonitrile (150 ml) was added to 25.00 g of methyl 4-(bromomethyl)benzoate, 19.02 g of potassium fluoride and 9.51 g of calcium fluoride, and the mixture was heated to reflux for 3 days. The reaction solution was concentrated. After addition of 200 ml of acetonitrile, insolubles were removed by filtration, and the filtrate was concentrated again. The residue was purified by silica gel column chromatography (YMC•GEL® SIL-60-230/70, n-hexane:ethyl acetate=10:1–4:1), followed by distillation under reduced pressure to provide 14.45 g of the objective compound as colorless oil. B.p. 118.5–119° C./18 mmHg. the mixture was heated to reflux for 3 days The reaction solution was concentrated After addition of 200 ml of acetonitrile, insolubles were removed by filtration the filtrate was concentrated again The residue was purified by silica gel column chromatography (YMC•GEL® SIL-60-230/70, n-hexane:ethyl acetate=10:1–4:1) followed by distillation under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 200 ml of methanol, 8.68 g of methyl 4-(fluoromethyl)benzoate was dissolved, and 77 ml of aqueous solution of 1 N sodium hydroxide was added dropwise with stirring and cooling. The mixture was then stirred for 3.5 hours at room temperature. After the mixture was acidified with 1 N hydrochloric acid, the precipitated crystals were collected by filtration, and the filtrate was concentrated. The precipitated crystals were combined with the residue obtained by concentrating the filtrate, and water was added thereto. The mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to provide 7.47 g of the objective compound as colorless crystals. cooling The mixture was then stirred for 3.5 hours at room temperature the precipitated crystals were collected by filtration the filtrate was concentrated obtained by concentrating the filtrate, and water was added The mixture was extracted with ethyl acetate dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 200 ml of methanol, 8.68 g of methyl 4-(fluoromethyl)benzoate was dissolved, and 77 ml of aqueous solution of 1 N sodium hydroxide was added dropwise with stirring and cooling. The mixture was then stirred for 3.5 hours at room temperature. After the mixture was acidified with 1 N hydrochloric acid, the precipitated crystals were collected by filtration, and the filtrate was concentrated. The precipitated crystals were combined with the residue obtained by concentrating the filtrate, and water was added thereto. The mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to provide 7.47 g of the objective compound as colorless crystals. cooling The mixture was then stirred for 3.5 hours at room temperature the precipitated crystals were collected by filtration the filtrate was concentrated obtained by concentrating the filtrate, and water was added The mixture was extracted with ethyl acetate dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 200 ml of methanol, 8.68 g of methyl 4-(fluoromethyl)benzoate was dissolved, and 77 ml of aqueous solution of 1 N sodium hydroxide was added dropwise with stirring and cooling. The mixture was then stirred for 3.5 hours at room temperature. After the mixture was acidified with 1 N hydrochloric acid, the precipitated crystals were collected by filtration, and the filtrate was concentrated. The precipitated crystals were combined with the residue obtained by concentrating the filtrate, and water was added thereto. The mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to provide 7.47 g of the objective compound as colorless crystals. M.p. 192–194° C. cooling The mixture was then stirred for 3.5 hours at room temperature the precipitated crystals were collected by filtration the filtrate was concentrated obtained by concentrating the filtrate, and water was added The mixture was extracted with ethyl acetate dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dry acetonitrile (150 ml) was added to 25.00 g of methyl 4-(bromomethyl)benzoate, 19.02 g of potassium fluoride and 9.51 g of calcium fluoride, and the mixture was heated to reflux for 3 days. The reaction solution was concentrated. After addition of 200 ml of acetonitrile, insolubles were removed by filtration, and the filtrate was concentrated again. The residue was purified by silica gel column chromatography (YMC•GEL® SIL-60-230/70, n-hexane:ethyl acetate=10:1–4:1), followed by distillation under reduced pressure to provide 14.45 g of the objective compound as colorless oil. B.p. 118.5–119° C./18 mmHg. the mixture was heated to reflux for 3 days The reaction solution was concentrated After addition of 200 ml of acetonitrile, insolubles were removed by filtration the filtrate was concentrated again The residue was purified by silica gel column chromatography (YMC•GEL® SIL-60-230/70, n-hexane:ethyl acetate=10:1–4:1) followed by distillation under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 200 ml of methanol, 8.68 g of methyl 4-(fluoromethyl)benzoate was dissolved, and 77 ml of aqueous solution of 1 N sodium hydroxide was added dropwise with stirring and cooling. The mixture was then stirred for 3.5 hours at room temperature. After the mixture was acidified with 1 N hydrochloric acid, the precipitated crystals were collected by filtration, and the filtrate was concentrated. The precipitated crystals were combined with the residue obtained by concentrating the filtrate, and water was added thereto. The mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to provide 7.47 g of the objective compound as colorless crystals. M.p. 192–194° C. cooling The mixture was then stirred for 3.5 hours at room temperature the precipitated crystals were collected by filtration the filtrate was concentrated obtained by concentrating the filtrate, and water was added The mixture was extracted with ethyl acetate dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dry acetonitrile (150 ml) was added to 25.00 g of methyl 4-(bromomethyl)benzoate, 19.02 g of potassium fluoride and 9.51 g of calcium fluoride, and the mixture was heated to reflux for 3 days. The reaction solution was concentrated. After addition of 200 ml of acetonitrile, insolubles were removed by filtration, and the filtrate was concentrated again. The residue was purified by silica gel column chromatography (YMC.GEL® SIL-60-230/70, n-hexane:ethyl acetate=10:1–4:1), followed by distillation under reduced pressure to provide 14.45 g of the objective compound as colorless oil. B.p. 118.5–119° C./18 mmHg. the mixture was heated to reflux for 3 days The reaction solution was concentrated After addition of 200 ml of acetonitrile, insolubles were removed by filtration the filtrate was concentrated again The residue was purified by silica gel column chromatography (YMC.GEL® SIL-60-230/70, n-hexane:ethyl acetate=10:1–4:1) followed by distillation under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 200 ml of methanol, 8.68 g of methyl 4-(fluoromethyl)benzoate was dissolved, and 77 ml of aqueous solution of 1 N sodium hydroxide was added dropwise with stirring and cooling. The mixture was then stirred for 3.5 hours at room temperature. After the mixture was acidified with 1 N hydrochloric acid, the precipitated crystals were collected by filtration, and the filtrate was concentrated. The precipitated crystals were combined with the residue obtained by concentrating the filtrate, and water was added thereto. The mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to provide 7.47 g of the objective compound as colorless crystals. M.p. 192–194° C. cooling The mixture was then stirred for 3.5 hours at room temperature the precipitated crystals were collected by filtration the filtrate was concentrated obtained by concentrating the filtrate, and water was added The mixture was extracted with ethyl acetate dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure